1. Field of the Invention
The present invention relates to methods for medical diagnosis and treatment, and more particularly to methods for diagnosis and treatment of specific psychiatric, neurological and neuroendocrine conditions using a Focused Ultrasonic Pulse (FUP) delivered to different points of neuronal circuits within the brain using existing focused ultrasound devices. The treatment is performed under the guidance of the existing brain-imaging devices, such as functional magnetic resonance imaging (fMRI).
2. Brief Description of the Prior Art
With advances in brain imaging techniques, the pathophysiology of psychiatric and medical disorders began to be more and more related to the specific neuronal circuits. Neuronal circuits are specific brain centers functionally and anatomically connected with each other. Usually a circuit involves sub-cortical neuronal centers connected with cortex. It is not totally clear how the circuits operate. However, it is clear that they play a major role in multiple psychiatric, neurological and medical conditions. For example, Obsessive Compulsive Disorder (OCD) and OCD Spectrum Disorders including Impulse Control Disorders appear to be related to abnormality in Orbito-Fronto-Talamic-Striatum circuit. Panic Disorder, Social Anxiety Disorder and panic spectrum disorders seem to be associated with the abnormal functioning of circuit involving Orbital-Frontal cortex, Amygdala, Cingulum and Hippocampus. Post-Traumatic Stress Disorders seem to associate with Prefrontal Cortex, Amydgala and Hippocampus abnormalities. Psychotic disorders seem to have an association with Prefrontal Cortex-Talamic-Striatum and Occipital Cortex Circuits. Circuits involved in neurological conditions have also been identified. For example, Parkinsonian Disease, Huntington Chorea, La Touretts and tick syndromes seem to have abnormalities in Cortico-Talamic-Straitum Circuit. Chronic pain has association with cortico-thalamic circuits. Insomnia has association with temporal cortex-lymbic-cingulum circuit. Medical conditions seem to have connection with specific neurocircuitry. For example, obesity and stress are associated with temporal-hypothalamic circuit. For a simple review and description of the above circuits, see Clark, D. L. and Boutros, N. N., Brain and Behavior (1999) and Rauch, S. L. et al., “Clinical Neuroimaging in Psychiatry” in Harvard Review of Psychiatry (1995), Vol. 2, no. 6, pp. 297-312.
Neuroimaging techniques exist that permit assessment of rapid changes in activity of the brain. Functional Nuclear Magnetic Resonance (fMRI), Vector Electroencephalagraphy (V-EEG) and Positron Emission Tomography (PET) are the most promising. These techniques, specifically fMRI, are capable of producing real time 3-dimensional maps of brain activity. These techniques merit scientists to study the neuronal circuits involved in pathology of different psychiatric or neurological conditions. However, the study process has been slowed by the absence of reliable activation of these circuits.
Recently, a few novel methods of the treatment of mental and neurological disorders directed at neuronal circuits have been introduced. These include deep brain stimulation by implanted electrodes, successfully used in OCD, Parkinson's disease and epilepsy, and brain surgery used in the treatment of OCD and depression. See New England Journal of Medicine (Sep. 27, 2001), pp. 656-63; R. M. Roth, et al., Current Psychiatry Report (October 2001), Vol. 3, no. 5, pp. 366-72. Because of the invasiveness and possible complications, these methods are reserved for the treatment resistant conditions where other treatments fail. However, the success of these treatments underlines the importance of specific neurocircuits in the pathophysiology of mental and neurological disorders. Furthermore, it underlines the importance of developing noninvasive methods of intervention at the neuronal circuit level. In addition, the studies using deep brain stimulation techniques determined that low frequency (2-150 Hz) signals inhibit the neuronal tissue and that high frequency (1-3 MHz) signals stimulate neuronal circuits.
Recently it has been proposed that neuronal circuits can be assessed and modified non-invasively using Transcranial Magnetic Stimulation (TMS). The signal from the brain after the TMS stimulation can be read using MRI. That method has been described in U.S. Patent No. 6,198,958, incorporated herein by reference, which described using the method for therapeutic purposes. The method and device proposed by that patent are currently being implemented in psychiatry and neurology for diagnostic and therapeutic purposes. See M.S. George, et al., Journal of Neuropsychiatry and Clinical Neuroscience (Fall 1996), Vol. 8, no. 4, pp. 373-382. The method, however, has several problems. For example, TMS does not stimulate deep brain centers, because it is incapable of penetrating brain tissue deeper than 1-2 cm. Also, TMS has a large area of focus, 1 cubic cm or more, which does not permit focused activation of a specific neuronal circuit. Also, there is a problem in using TMS together with fMRI, because TMS produces a magnetic signal that interferes with the magnetic field and consequently with the fMRI image.
Focused ultrasound has been used to modify electrical currents in neuronal tissue. This has been done by a combined application of a magnetic field and an ultrasonic field to neuronal and other tissue in the body. The prior art proposes that modification of electrical currents in neuronal tissue will come from the interaction of the two fields. For example, U.S. Pat. No. 4,343,301 describes generating high energy by intersecting two ultrasound beams within any single fixed point of the body, including the skull. While it is not proven that such an application of ultrasound would do anything except heat or destroy tissue, there is recent evidence that application of focused ultrasound to brain slices, subjected to simultaneous electrical stimulation, can change the electrical currents in the slices. However, because two ultrasound beams cannot be focused within the skull, because of the complexity of bone density and bone structure, it is not possible to focus such a two-beam device in the brain tissue.
Some companies have produced ultrasonic devices that use multiple beams. See G. T. Clement, et al., Physics in Medicine and Biology (December 2000), Vol. 45, no. 12, pp. 3707-3719. By coordinating the amplitude and the phase of the ultrasound beams generated by multiple sources via computer multi-beam devices, algorithms can be developed to adjust the bone dispersion of the beam and focus the ultrasound within the brain tissue. These devices are to be used as ultrasonic knives within the brain for the destruction of tumors, for example. However, they cannot be used to modify the electrical and electromagnetic currents within the brain circuits without harming the surrounding tissue.